Bruno Palmentieri

Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels

BACKGROUND & AIMS Some patients with serum hepatitis C virus (HCV) have persistently normal aminotransferase (ALT) levels and are affected by cirrhosis. This study prospectively evaluated progression of the disease in a group of anti-HCV-positive patients with persistently normal ALT levels. METHODS Thirty-seven subjects were studied. Each subject underwent liver biopsy at baseline and after 5 years of follow-up. At baseline, serum samples were tested for genotypes and HCV RNA load. ALT levels and serum HCV RNA were tested every other month and every 6 months, respectively. Patients with increased ALT were discharged from the study and treated with IFN. Five years after the end of IFN therapy, a liver biopsy was performed. RESULTS Liver biopsy at baseline showed chronic hepatitis in 34 patients and normal histology in 3 patients, 2 of whom were negative for HCV RNA and 1 positive. HCV genotypes were distributed as follows: 2a, 56%; 1b, 41%; and 1a, 3%. At the end of 7-year follow-up, 73% of the patients still had normal ALT values. Liver histology after 5 years was comparable to that observed at entry to study. CONCLUSIONS Most patients with persistently normal ALT serum levels have very mild chronic hepatitis. However, healthy anti-HCV-positive subjects exist. In patients with HCV-related chronic hepatitis associated with persistently normal ALT levels, the grade of disease activity does not increase over years and progression to cirrhosis is slow or absent.

Diagnosis of chronic liver disease: reproducibility and validation of liver biopsy

at nucleotide 677) in the coding region of the gene for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation pathway of homocysteine. Recently, we performed a study in a population of 64 IBD patients in whom vitamin B12 and folic acid levels were determined together with the prevalence of the MTHFR genotypes. Among the 11 IBD patients carrying the TT MTHFR genotype, six had hyperhomocysteinemia, of whom five had concurrent folate and/or vitamin B12 deficiency. The relative risk of developing hyperhomocysteinemia was 5.3-fold (95% CI 2.9–9.6) in IBD patients with the TT MTHFR genotype associated with folate and/or vitamin B12 deficiency, in comparison to individuals with CC or CT MTHFR genotypes and adequate levels of folate and/or vitamin B12. Furthermore, in patients’ homozygotic for the C677T MTHFR gene mutation there is an increased folate requirement to mantain plasma homocysteine within normal levels (5). Thus, the IBD patients with this genetic background are at increased risk to develop hyperhomocysteinemia and may need vitamin B12 and folate supplementation. In conclusion, we suggest that determination of both the MTHFR genotype and vitamin status may predict the risk of developing hyperhomocysteinemia in IBD patients.

Prevalence and incidence of cryoglobulins in hepatitis C virus-related chronic hepatitis patients: a prospective study.

OBJECTIVES:A high prevalence of cryoglobulins has been reported in patients with hepatitis C virus (HCV)-related liver disease. The aim of this study was to evaluate the prevalence and the incidence of cryoglobulins and their association with clinical symptoms in chronic hepatitis and cirrhosis patients.METHODS:The prevalence of cryoglobulins and cryoglobulinemic syndrome was investigated at enrollment in 237 patients (213 with chronic hepatitis and 24 with cirrhosis). A 7-yr follow-up was conducted evaluating the occurrence of cryoglobulins and/or cryoglobulinemic syndrome every 6 months. Rheumatoid factor was also tested in all patients.RESULTS:Prevalence of rheumatoid factor, cryoglobulins, and cryoglobulinemic syndrome in chronic hepatitis patients were 2%, 0.8%, and 0%, respectively. In cirrhosis patients the prevalence was 4%, 8%, and 0%, respectively. No statistically significant differences were found between the two groups. During the follow-up only one patient for each group abruptly developed cryoglobulinemic syndrome, and none of the patients who showed signs of cryoglobulinemia developed the syndrome or showed signs of evolution of the disease.CONCLUSIONS:Our data demonstrate that the presence of cryoglobulins and/or cryoglobulinemic syndrome in HCV-related liver disease is unusual, as is the occurrence of cryoglobulinemia over time in these patients. This leads us to think that HCV-related cryoglobulinemic syndrome and HCV-related liver disease are independent diseases. This supports new and indirect evidence for an independent and direct role of HCV in liver and blood disorders.

Which clinical and sonographic parameters may be useful to discriminate NASH from steatosis

Background The natural history of nonalcoholic steatohepatitis (NASH) includes the passage through steatosis. Goal To retrospectively evaluate the usefulness of sonographic parameters compared to histological diagnosis when differentiating steatosis from NASH. Study This retrospective study reviewed records of patients with steatosis from databases of our Departments, selecting only those who had been diagnosed by sonography and liver biopsy [64 males (63.82%); 30 females (36.18%)]. Results Attenuation of the echo amplitude (P<0.05; odds ratio (OR): 3.43; confidence interval (CI): 1.02-11.57), focal fat sparing (P<0.05; OR: 3; CI: 1.02-11.88) and splenic diameter (P<0.05; OR: 1.66; CI: 1.04-3.26) were independent predictors of NASH. A significantly higher association of attenuation of the echo amplitude, enlarged splenic diameter, and presence of focal fat sparing was observed in NASH patients (P<0.01). Conclusions It is very difficult to build a predictive system to distinguish NASH from steatosis based on sonographic scores. However, it is already possible to differentiate NASH from steatosis by combining 3 simple sonographic parameters: attenuation of the echo amplitude, enlarged splenic diameter, and presence of focal fat sparing.

CASE REPORT: Occurrence of HCC in Asymptomatic HCV-Related Chronic Hepatitis

Patients with persistently normal ALT affected with HCV-related chronic hepatitis exist. The natural history of liver disease in these patients was demonstrated to be very slow and progression to cirrhosis likely absent. The case we report describes the occurrence of hepatocellular carcinoma (HCC) in a patient with persistently normal ALT affected with mild chronic hepatitis. This observation suggests that asymptomatic carriers of HCV may develop HCC that is not related to underlying liver cirrhosis.